In a current model, Wnt signaling initially
leads to a complex between Dsh, GBP/Frat1, Axin and Zw3/GSK,
which may be the regulatory step in the inactivation of Zw3/GSK(Salic,
2000; Farr
2000).The DIX domain in Axin is similar to the NH2 terminus in Dsh, and promotes interactions between Dsh and Axin (Hsu 1999,Smalley,
1999). As a consequence, GSK does not phosphorylate b-catenin anymore, releasing it from the Axin complex and accumulation (Salic,
2000).The stabilized b-catenin then enters the nucleus to interact with TCF. b-catenin can convert TCF into a transcriptional activator of the same genes that are repressed by TCF alone (reviewed in Nusse, 1999). Two other key players in this complex are Legless (Bcl9) and Pygopos (Kramps 2002, Thompson 2002, Parker 2002). In mammalian cells and in the Zebrafish, Bcl9-2 regulates binding of b-catenin to the adhesion complex or its presence in the nucleus, by interacting with the tyrosine phosphorylated form of b-catenin (Brembeck, 2004).

Activating mutations in the human b-catenin gene have been found in human colon cancer and melanomas (Morin et al, 1997) These mutations alter specific b-catenin residues important for GSK3 phosphorylation and stability. There is a separate list of mutations.

Vertebrates have two Armadillo/b-catenin homologs, b-catenin and plakoglobin (also called gamma-catenin). It is not clear whether plakoglobin is mutated in cancer, although overexpression of mutant forms can transform cells (Kolligs, 2000) . Both plakoglobin and b-catenin bind to cadherins to establish cell adhesion.

There are three b-catenin genes in C. elegans. Interestingly, one of them (HMP-2) is dedicated to adhesion only, whereas BAR-1 and WRM-1 act in Wnt signaling(Korswagen 2000Natarajan 2001)Schneider et al (2003) postulate that a single, b-catenin gene fulfilled both adhesion and signaling functions in the last common ancestor of metazoans some 700 million years ago.